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Single dose intravenous pharmacokinetics of fluconazole in infants
I Krzeska1, R A Yeates, G Pfaff
1Clinic for Infants and Metabolic Diseases, Warsaw, Poland.
Insights
This study examined fluconazole pharmacokinetics in infants, finding a larger volume of distribution and higher clearance compared to adults. These factors influence fluconazole
Area of Science:
- Pharmacology
- Pediatric Medicine
- Infectious Diseases
Background:
- Fungal infections pose a significant risk to infants.
- Understanding drug pharmacokinetics in neonates and infants is crucial for effective treatment.
- Fluconazole is a widely used antifungal agent.
Purpose of the Study:
- To determine the plasma pharmacokinetics of fluconazole in infants.
- To compare fluconazole's pharmacokinetic parameters in infants versus adult volunteers.
- To investigate the impact of age on fluconazole distribution and elimination.
Main Methods:
- An open, non-comparative study was conducted.
- A single intravenous dose of fluconazole (3 mg/kg) was administered.
- Plasma samples were analyzed to determine pharmacokinetic parameters in 14 infants (9 days to 4.4 months old).
Main Results:
- The mean volume of distribution in infants was 1.17 L/kg, significantly higher than the adult value of 0.65 L/kg.
- Mean total clearance in infants was 0.63 mL/min/kg, also higher than the adult value of 0.25 mL/min/kg.
- The terminal half-life of elimination was 22.5 hours in infants, compared to 30.2 hours in adults.
Conclusions:
- Infants exhibit distinct fluconazole pharmacokinetics compared to adults, characterized by increased volume of distribution and clearance.
- Age-related changes in clearance and volume of distribution likely explain the observed pharmacokinetic differences.
- These findings are essential for optimizing fluconazole dosing strategies in pediatric populations.
Abstract:
The present report contains an open, non-comparative study of the plasma pharmacokinetics of a single intravenous dose (3 mg/kg) of the antimycotic agent fluconazole in infants, aged between 9 days and 4.4 months (n = 14), who were either suffering from or regarded as being susceptible to fungal infection. The mean volume of distribution was calculated as 1.17 l/kg, with a range between 0.76 and 2.60 l/kg; the comparable value for adult volunteers was 0.65 +/- 0.08 l/kg (1). The mean total clearance was calculated as 0.63 +/- 0.06 ml/min x kg; the comparable value for adult volunteers was 0.25 +/- 0.04 ml/min x kg (1). The terminal half-life of elimination was calculated as 22.5 +/- 2.2 h; the comparable value for adult volunteers was 30.2 +/- 3.8 h (1). It is suggested that this difference was caused by the countervailing effects of the changes with age in clearance and in volume of distribution.